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PubMed1983

Eating, drinking and urine output after prolonged cerebroventricular vasopressin infusions in rats.

Prior studies suggested that centrally administered single doses of vasopressin (VP) do not affect consummatory behavior or peripheral hydration. To reduce uncertainties related to factors of unknown distribution, concentration and duration, we infused VP (0.5 or 50 ng/h) continuously for 5 h or 5 days into a lateral cerebroventricle of conscious male rats. Eating and drinking behavior, as well as urine volume and sodium and potassium output, were unaffected by these treatments. The results suggest that VP, at sites reached from cerebrospinal fluid, does not alter peripheral hydration of rats.

Animals↗

PubMed1996

Natriuresis following central and peripheral administration of agmatine in the rat.

Agonists specific for the I1 imidazoline receptor increase sodium excretion following intrarenal (ir) infusion or intracerebroventricular (icv) injection in the rat. Although agmatine has been suggested to be a putative endogenous agonist for these receptors, the ability of this compound to alter sodium excretion has not been determined. The effects of agmatine, whether administered ir or icv, on blood pressure and solute and water excretion were studied in Sprague-Dawley rats. Agmatine was administered by icv injection (0, 10, 100, 300 or 1,000 nmol in 5 microliters) or by direct ir infusion (0, 3, 10, 30 or 100 nmol/kg/min at 3.4 microliters/min) in pentobarbitone-anesthetized rats. Agmatine administered by icv injection or ir infusion did not alter blood pressure or heart rate. Only an ir infusion of agmatine produced an increase in creatinine clearance, which occurred at the lowest (3 nmol/kg/min) and highest dose (100 nmol/kg/min). Concomitantly, the ir infusion of agmatine produced a dose-related increase in urine flow rate, but both routes of administration were associated with an increase in sodium excretion and osmolar clearance. Similar to previous reports with I1 imidazoline receptor-selective compounds, agmatine increased urine flow rate secondary to an increase in osmolar clearance at doses that failed to alter blood pressure. These results were consistent with agmatine functioning as a physiological agonist resulting in alterations in sodium excretion.

Agmatine↗

PubMed1997

Differential effect of central versus parenteral administration of morphine sulfate on regional concentrations of reduced glutathione in rat brain.

Prior studies in rodents have shown significant depletion of reduced glutathione (GSH) in peripheral organs following acute systemic or central administration of opioids. However, little information exists on whether opioid administration affects concentrations of brain GSH. Recently, clinical observations have indicated acute declines of GSH concentrations in the cerebrospinal fluid of cancer patients after acute intracerebroventricular (ICV) morphine which may contribute to the development of organic behavioral brain syndromes associated with central opioid analgesia. Collectively these data led us to investigate the affect of acute systemic and central morphine on regional concentrations of GSH in rat brain. Systemic morphine had no effect on GSH concentrations in selected brain areas. In contrast, ICV morphine resulted in selective GSH depletion in the caudate nucleus, consistent with concurrent excitatory locomotive behavior. This change may have reflected morphine-induced oxidative stress together with increased metabolic activity within the extrapyramidal system.

Analgesics, Opioid↗

PubMed2003

Renal sympathetic nerve responses to tempol in spontaneously hypertensive rats.

Recent studies have implicated a contribution of oxidative stress to the development of hypertension. Studies were performed to determine the effects of the superoxide dismutase (SOD) mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol) on vascular superoxide production and renal sympathetic nerve activity (RSNA) in anesthetized Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Compared with WKY rats (n=6), SHR showed a doubled vascular superoxide production, which was normalized by treatment with Tempol (3 mmol/L, n=7). In WKY rats (n=6), Tempol (30 mg/kg IV) significantly decreased mean arterial pressure (MAP) from 108+/-5 to 88+/-6 mm Hg and HR from 304+/-9 to 282+/-6 beats/min. In SHR (n=6), Tempol significantly decreased MAP from 166+/-4 to 123+/-9 mm Hg and HR from 380+/-7 to 329+/-12 beats/min. Furthermore, Tempol significantly decreased RSNA in both WKY rats and SHR. On the basis of group comparisons, the percentage decreases in MAP (-28+/-4%), HR (-16+/-3%) and integrated RSNA (-63+/-6%) in SHR were significantly greater than in WKY rats (-17+/-3%, -9+/-2%, and -30+/-4%, respectively). In SHR, changes in integrated RSNA were highly correlated with changes in MAP (r=0.85, P<0.0001) during administration of Tempol (3, 10, and 30 mg/kg IV). In both WKY rats and SHR (n=4, respectively), intracerebroventricular injection of Tempol (300 micro g/1 micro L) did not alter MAP, HR, or RSNA. Intravenous administration of a SOD inhibitor, diethyldithio-carbamic acid (30 mg/kg), significantly increased MAP, HR, and integrated RSNA in both WKY rats and SHR (n=6, respectively). These results suggest that augmented superoxide production contributes to the development of hypertension through activation of the sympathetic nervous system.

Animals↗

PubMed1987

Central dopaminergic regulation of aldosterone secretion in sheep.

Central dopaminergic mechanisms involved in the regulation of plasma aldosterone concentration were investigated in 16 conscious sheep following Na depletion with intramuscularly administered furosemide. Intracerebroventricular infusion of dopamine (20 micrograms/min) decreased plasma aldosterone significantly to 52 +/- 8% of basal level and increased plasma renin activity (PRA) significantly to 172 +/- 25% of basal level in this animal model. In addition, intracerebroventricular infusion of the dopamine antagonist metoclopramide (20 micrograms/min) in artificial cerebrospinal fluid vehicle significantly increased aldosterone levels to 144 +/- 14% of basal level and decreased PRA to 62 +/- 5% of basal value. Neither intracerebroventricular infusion of the vehicle nor intravenous infusions of metoclopramide or dopamine at the same doses changed aldosterone or PRA levels. Intracerebroventricular bolus injections of metoclopramide (20 micrograms/kg in 0.4 ml of vehicle) were also effective, increasing aldosterone levels to 266 +/- 22% of basal level and decreasing PRA to 70 +/- 12% of basal level. Intravenous bolus injections of the same dose of metoclopramide were ineffective. Dopamine was infused intracerebroventricularly into two uniadrenalectomized sheep with the remaining adrenal transplanted to the neck. Aldosterone levels were decreased to 49 +/- 10% of basal level, and PRA was increased to 157 +/- 10% of basal value. None of the infusions or injections changed arterial or intracranial pressure, or plasma K, Na, and cortisol levels. These data indicate that endogenous or exogenous dopamine may act on central dopamine receptors to decrease plasma aldosterone concentration by an unknown humoral mechanism. The known aldosterone regulators, plasma Na, K, angiotensin II, and adrenocorticotropic hormone, are not involved in the regulation.

Adrenal Glands↗

PubMed1992

Centrally infused bradykinin increases baroreceptor reflex sensitivity.

Kinins are present in the central nervous system, and central administration of bradykinin increases blood pressure and heart rate. In this study, we determined the effect of intracerebroventricular infusion of bradykinin on the baroreceptor reflex of conscious rats. Male Wistar rats were anesthetized with thiobarbital (40 mg/kg i.p.), and chronic intracerebroventricular cannulas (25 gauge) were implanted into the lateral ventricles. Baroreceptor control of heart rate was evaluated by recording reflex heart rate changes (beats per minute) in response to mean arterial pressure changes (mm Hg) produced by bolus injection of phenylephrine (0.5-20 micrograms/kg i.v.) or sodium nitroprusside (0.5-25 micrograms/kg i.v.). The ratio beats per minute/mm Hg or the mean slope of the individual regression lines of the relation between heart rate and mean arterial pressure changes for increases or decreases in arterial pressure was used as an index of baroreceptor reflex sensitivity. Baroreceptor control of heart rate was evaluated within 1 and 3 hours of intracerebroventricular infusion of bradykinin (7.5 micrograms/7 microliters/hr) or saline (7 microliters/hr). There was no change in basal mean arterial pressure or heart rate during central bradykinin infusion (112 +/- 2 mm Hg and 402 +/- 18 beats per minute in the control period). After 1 hour of central bradykinin infusion, there was a significant increase of baroreceptor reflex sensitivity for increments in mean arterial pressure (-2.91 +/- 0.26 versus -1.5 +/- 0.24 beats per minute/mm Hg in the control period; p less than 0.01, paired Student's t test). In contrast, no significant changes were observed for the reflex tachycardia. Similar results were obtained with 3 hours of infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Chronic central versus peripheral ouabain, blood pressure, and sympathetic activity in rats.

To assess whether chronic ouabain administration causes hypertension by increasing sympathetic activity, we recorded arterial blood pressure and heart rate at rest and after ganglionic blockade in conscious Wistar rats following 10 to 14 days of central or peripheral administration of ouabain. Intracerebroventricular or intravenous infusion of ouabain (10 micrograms/d for both) as well as subcutaneous ouabain pellets (releasing 25 micrograms ouabain/d per pellet) increased mean arterial pressure by 20 to 30 mm Hg and heart rate by 40 to 60 beats per minute. Ouabain pellets increased blood pressure and heart rate in a dose-related manner. After 2 weeks of all ouabain treatments, ouabainlike activity in plasma was not changed but increased significantly in hypothalamus and adrenals. Ouabainlike activity in the adrenals was increased more by intravenous than subcutaneous or intracerebroventricular ouabain treatment, but the different treatment modes caused similar increases in the hypothalamus. Concomitant central infusion of antibody Fab fragments against ouabain prevented the ouabain pellet-induced increases in blood pressure and heart rate. Ganglionic blockade by intravenous hexamethonium normalized blood pressure and heart rate in ouabain-treated rats. These data suggest that in normotensive rats exogenous ouabain, regardless of the mode of administration, may act centrally to cause sympathoexcitation and thus hypertension.

Animals↗

PubMed1999

Interactions between the melanocortin system and leptin in control of sympathetic nerve traffic.

Leptin plays an important role in regulation of body weight through regulation of food intake and sympathetically mediated thermogenesis. The hypothalamic melanocortin system, via activation of the melanocortin-4 receptor (MC4-R), decreases appetite and weight, but its effects on sympathetic nerve activity (SNA) are unknown. In addition, it is not known whether sympathoactivation to leptin is mediated by the melanocortin system. We tested the interactions between these systems in regulation of brown adipose tissue (BAT) and renal and lumbar SNA in anesthetized Sprague-Dawley rats. Intracerebroventricular administration of the MC4-R agonist MT-II (200 to 600 pmol) produced a dose-dependent sympathoexcitation affecting BAT and renal and lumbar beds. This response was completely blocked by the MC4-R antagonist SHU9119 (30 pmol ICV). Administration of leptin (1000 microg/kg IV) slowly increased BAT SNA (baseline, 41+/-6 spikes/s; 6 hours, 196+/-28 spikes/s; P=0.001) and renal SNA (baseline, 116+/-16 spikes/s; 6 hours, 169+/-26 spikes/s; P=0.014). Intracerebroventricular administration of SHU9119 did not inhibit leptin-induced BAT sympathoexcitation (baseline, 35+/-7 spikes/s; 6 hours, 158+/-34 spikes/s; P=0.71 versus leptin alone). However, renal sympathoexcitation to leptin was completely blocked by SHU9119 (baseline, 142+/-17 spikes/s; 6 hours, 146+/-25 spikes/s; P=0.007 versus leptin alone). This study demonstrates that the hypothalamic melanocortin system can act to increase sympathetic nerve traffic to thermogenic BAT and other tissues. Our data also suggest that leptin increases renal SNA through activation of hypothalamic melanocortin receptors. In contrast, sympathoactivation to thermogenic BAT by leptin appears to be independent of the melanocortin system.

Adipose Tissue, Brown↗

PubMedDate not supplied

Modulation of brain angiotensin-converting enzyme by dietary sodium and chronic intravenous and intracerebroventricular fusion of angiotensin II.

Angiotensin-converting enzyme (ACE) in rat brain closely resembled that in lung in its kinetics with the substrate Hip-His Leu, the inhibitors SQ 20,881 and SQ 14,225, and iun its Cl- activation profile. Modification of dietary NaCl intake was associated with marked changes in brain ACE activity. Sodium-loaded rats had lower activity of ACE in hypothalamus, striatum, and midbrain, and higher activity in spinal cord compared to controls. In sodium-restricted rats, ACE was elevated in pituitary and depressed in spinal cord. Chronic intravenous infusion of angiotensin (AII) was associated with a pattern of changes partly resembling sodium loading: ACE was depressed in hypothalamus and striatum but elevated in midbrain. After chronic intracerebroventricular infusion of AII, ACE was elevated in striatum and hippocampus, and depressed in spinal cord; a pattern of changes quite different from those associated with intravenous AII. These results show that ACE in several brain regions is sensitive to dietary sodium intake and support the hypothesis that angiotensin-containing neurons in these areas might be responsive to NaCl status of the animal. The observed changes in brain ACE do not seem to be explained in any simple manner by changes in circulating or central angiotensin II.

Angiotensin II↗

PubMedDate not supplied

Central pressor action of neurotensin in conscious rats.

The effects of neurotensin upon blood pressure in conscious rats were examined after intracerebroventricular (i.v.t.) or intravenous (i.v.) administration of this peptide. Whereas i.v. injected neurotensin (0.1-2.0 microgram/kg) was depressor, i.v.t. injected neurotensin (1 microgram and above) was pressor. Peripheral depressor responses could not be repeated in the same animal due to tachyphylaxis, but central pressor responses were repeatable without reduction in magnitude, showing that the two effects were separate entities. Thyrotropin-releasing hormone (TRH), which is reported to be a potent neurotensin antagonist, completely abolished the neurotensin depressor response, and attenuated the central pressor action. TRH did not alter the central pressor effect of another peptide, angiotensin II (AII). The potent AII receptor antagonist saralasin, while abolishing the central pressor effect of AII, was completely without effect upon the neurotensin-induced pressor response. These results indicate that i.v.t. injected neurotensin and AII stimulate a rise in blood pressure via different receptors. The alpha-adrenergic antagonists phentolamine, prazosin, or yohimbine (injected i.v.t.) involvement of the sympathetic nervous system in this response. These results are discussed in relation to the central pressor actions of other neuropeptides.

Animals↗

PubMed2004

Hypertension caused by angiotensin II infusion involves increased superoxide production in the central nervous system.

Hypertension caused by angiotensin II (Ang II) infusion is associated with oxidative stress in the peripheral vasculature and kidney. The role of redox mechanisms in the central nervous system (CNS), a tissue known to be pivotal in Ang II-dependent hypertension, has not been investigated. We recently identified superoxide (O2*-) in the brain as a key signaling intermediate in the transient pressor response elicited by acute injection of Ang II directly into the CNS. Here we tested the hypothesis that hypertension caused by chronic systemic infusion of Ang II is mediated by a central neurogenic mechanism involving O2*-. Infusion of Ang II (600 ng x kg(-1) x min(-1)) over a 2-week period in mice caused a gradually developing hypertension that was correlated with marked elevations in O2*- production specifically in the subfornical organ (SFO), a brain region lying outside the blood-brain barrier and known to be a primary sensor for blood-borne Ang II. Adenoviral-mediated delivery of cytoplasmically targeted superoxide dismutase (SOD) selectively to this site prevented the hypertension and the increased O2*- production, whereas gene transfer of SOD targeted to the extracellular matrix had no effect. These data suggest that increased intracellular O2*- production in the SFO is critical in the development of Ang II-induced hypertension.

Adenoviridae↗

PubMed1999

Blockade of central angiotensin AT(1) receptors improves neurological outcome and reduces expression of AP-1 transcription factors after focal brain ischemia in rats.

BACKGROUND AND PURPOSE: Angiotensin-converting enzyme inhibitors have been shown to protect against stroke in hypertensive rats and to improve neurological outcome after cerebral ischemia in normotensive rats. The present study was designated to test the hypothesis that blockade of brain AT(1) receptors improves the recovery from focal cerebral ischemia and reduces expression of AP-1 transcription factors c-Fos and c-Jun, which have been associated with programmed cell death and neurodegeneration. METHODS: Experiments were carried out in normotensive male Wistar rats. Focal cerebral ischemia was induced by middle cerebral artery occlusion lasting for 90 minutes and followed by reperfusion. The selective AT(1) receptor antagonist irbesartan was infused intracerebroventricularly over a 5-day period before the induction of ischemia at a dose that inhibited brain but not vascular AT(1) receptors. Twenty-four hours after ischemia, neurological outcome was evaluated and expression of c-Fos and c-Jun proteins in the brain was studied immunocytochemically. RESULTS: Focal brain ischemia resulted in a strong induction of c-Fos and c-Jun proteins in the cortex, which positively correlated with the degree of neurological deficits. Treatment of rats with irbesartan significantly improved neurological outcome of focal cerebral ischemia when compared with the vehicle-treated group and markedly reduced the expression of c-Fos and c-Jun proteins in the cortex on the ligated side of the brain. Irbesartan pretreatment completely abolished the ischemia-induced c-Fos expression in the hippocampus. CONCLUSIONS: The present study shows a relationship between c-Fos and c-Jun expression and neurological outcome after focal brain ischemia. Our data indicate that long-term blockade of central AT(1) receptors improves the recovery from brain ischemia and reduces the expression of c-Fos and c-Jun proteins in the brain. Pretreatment with an AT(1) receptor antagonist has beneficial effects after cerebral ischemia.

Analysis of Variance↗

PubMed1984

Control of cardiac output in thyrotoxic calves. Evaluation of changes in the systemic circulation.

The contribution of peripheral vascular factors to the high output state in thyrotoxicosis was examined in 11 calves treated with daily intramuscular injections of L-thyroxine (200 micrograms/kg) for 12-14 d. Thyroxine treatment increased cardiac output from 14.1 +/- 1.4 to 24.7 +/- 1.4 liters/min (P less than 0.001) and decreased systemic vascular resistance from 562 +/- 65 to 386 +/- 30 dyn-s/cm5 (P less than 0.01). Blood volume was increased from 65 +/- 4 ml/kg in the euthyroid state to 81 +/- 6 ml/kg when the animals were thyrotoxic (P less than 0.05). The role of low peripheral vascular resistance in maintenance of the high output state was evaluated by infusion of phenylephrine at two dosages (2.5 and 4.0 micrograms/kg per min). In the euthyroid state, no significant decrease in cardiac output was observed at either level of pressor infusion. In the thyrotoxic state, the higher dosage of phenylephrine increased peripheral resistance to the euthyroid control level and caused a small (6%) decrease in cardiac output (P less than 0.05). This small decrease in cardiac output probably could be attributed to the marked increase in left ventricular afterload caused by the pressor infusion as assessed from measurements of intraventricular pressure and dimensions. Changes in the venous circulation were evaluated by measurement of mean circulatory filling pressure and the pressure gradient for venous return in six animals during cardiac arrest induced by injection of acetylcholine into the pulmonary artery. Mean circulatory filling pressure increased from 10 +/- 1 mmHg in the euthyroid state to 16 +/- 2 mmHg (P less than 0.01) during thyrotoxicosis, while pressure gradient for venous return increased from 10 +/- 1 to 14 +/- 2 mmHg (P less than 0.02). These changes in venous return curves were not affected significantly by ganglionic blockade with trimethapan (2.0 mg/kg per min) before cardiac arrest. Thus, the high output state associated with thyrotoxicosis is not dependent upon a low systemic vascular resistance, but is associated with increases in blood volume, mean circulatory filling pressure, and pressure gradient for venous return.

Animals↗

PubMed1998

Central nervous system nitric oxide synthase activity regulates insulin secretion and insulin action.

Systemic inhibition of nitric oxide synthase (NOS) with NG-monomethyl-L-arginine (L-NMMA) causes acute insulin resistance (IR), but the mechanism is unknown. We tested whether L-NMMA-induced IR occurs via NOS blockade in the central nervous system (CNS). Six groups of Sprague-Dawley rats were studied after chronic implantation of an intracerebroventricular (ICV) catheter into the lateral ventricle and catheters into the carotid artery and jugular vein. Animals were studied after overnight food deprivation, awake, unrestrained, and unstressed; all ICV infusion of L-NMMA or D-NMMA (control) were performed with artificial cerebrospinal fluid. ICV administration of L-NMMA resulted in a 30% rise in the basal glucose level after 2 h, while ICV D-NMMA had no effect on glucose levels. Insulin, epinephrine, and norepinephrine levels were unchanged from baseline in both groups. Tracer (3H-3-glucose)-determined glucose disposal rates during 2 h euglycemic hyperinsulinemic (300 microU/ml) clamps performed after ICV administration of L-NMMA were reduced by 22% compared with D-NMMA. Insulin secretory responses to a hyperglycemic clamp and to a superimposed arginine bolus were reduced by 28% in L-NMMA-infused rats compared with D-NMMA. In conclusion, ICV administration of L-NMMA causes hyperglycemia via the induction of defects in insulin secretion and insulin action, thus recapitulating abnormalities observed in type 2 diabetes. The data suggest the novel concept that central NOS-dependent pathways may control peripheral insulin action and secretion. This control is not likely to be mediated via adrenergic mechanisms and could occur via nonadrenergic, noncholinergic nitrergic neural and/or endocrine pathways. These data support previously published data suggesting that CNS mechanisms may be involved in the pathogenesis of some forms of insulin resistance and type 2 diabetes independent of adiposity.

Animals↗

PubMed2006

Dopamine stimulation via infusion in the lateral ventricle.

Continuous dopamine (DA) stimulation is a therapeutic approach that applies to the treatment of motor fluctuations due to pulsatile DA stimulation in Parkinson's disease (PD), to cure the abuse of drugs, such as cocaine or amphetamine (which produce short-lasting peaks of extracellular DA), and as a safe therapeutic approach to avoid hedonistic homeostatic dysregulation (which sometime develops as an abuse pattern in PD patients receiving a pulsatile DA replacement therapy). However, systemic continuous delivery of DA agonists leads to a variety of side effects. In search for an alterative approach, in the present study we evaluated the possibility of delivering intracerebroventricularly (i.c.v.), a DA agonist: lisuride that was already shown to be effective when administered continuously subcutaneously (s.c.). In particular, we were interested in examining whether lisuride infused within the lateral ventricle was still able to stimulate DA receptor by inducing contralateral turning behavior in hemiparkinsonian rats. We found that lisuride, when infused in the lateral ventricle was effective in reducing the threshold for stimulating DA receptors. These results offer a more reliable and safe therapeutic approach to deliver continuous DA selectively in the brain.

Animals↗

PubMed1999

Water drinking in rats resulting from intravenous relaxin and its modification by other dipsogenic factors.

The purpose of the study was to determine whether iv infusion of relaxin would acutely stimulate water drinking in rats and, if it did, whether such drinking is affected by other dipsogenic stimuli or is blocked by centrally administered losartan. iv infusions of human gene 2 relaxin at doses of 25, 40, 55, or 80 microg/kg x h for 1 h induced dose-dependent water drinking in both male and female rats within 15-30 min of commencement of infusions. iv infusion of a nondipsogenic dose of angiotensin II (0.5 microg/h), combined with relaxin (40 microg/kg x h), almost tripled the relaxin-induced water intake. iv infusion of hypertonic (1 M) NaCl did not potentiate relaxin-induced drinking. Intracerebroventricular injection of the angiotensin AT1 antagonist losartan (10 microg) reduced water drinking induced by iv infusion of relaxin. The water drinking induced by iv infusion of relaxin in the rat suggests that blood-borne relaxin may be a dipsogenic hormone. Potentiation of this relaxin-induced drinking by moderate levels of circulating angiotensin II is additional evidence in support of this view. The results also indicate that a central angiotensinergic neural pathway, utilizing AT1 receptors, subserves relaxin-induced drinking.

Angiotensin II↗

PubMed1993

Neurotoxicology of chronic infusion of the ganglioside GM1 in the ewe: phase I. intrathecal administration.

Gangliosides, including GM1, provide a measure of improved functional recovery after ischemic, toxic, and traumatic brain injuries in animal studies. Since systemically injected GM1 has provided equivocal results in a variety of human neurodegenerative conditions, the possibility exists that intrathecal or intracerebroventricular delivery might provide more effective concentrations along the neuroaxis. In preparation to consider clinical trials, the potential neurotoxicologic effects of chronic intrathecal GM1 were studied in ewes. Preliminary in vitro tests first demonstrated the stability and compatibility of GM1 in implanted pumps. Two groups of adult ewes were then implanted with either Therex or Infusaid continuous flow implantable pumps and chronic intrathecal catheters. Ewes were infused intrathecally with either preservative-free normal saline (n = 5) or GM1 (n = 7) 100 micrograms-10,000 micrograms/d for up to 24 wk. No abnormal behavioral responses were noted. Cerebrospinal fluid analyzed for GM1 concentrations by thin layer chromatography revealed no evidence of GM1 accumulation. After the animals were killed, spinal cords were removed, fixed, sectioned, and stained. Histologic analysis revealed no generalized pattern of neuronal damage, demyelination, gliosis, or axonopathy to distinguish intrathecal normal saline or GM1. In both treated and control groups, the only consistent finding was a pericatheter-associated compression of white matter with axonal dilation, vacuolation, and occasional neuronal loss. Catheter tracts in both groups were also associated with variable leptomeningeal fibroproliferative changes in adjacent dura and pia, at times in conjunction with more generalized duromeningeal thickening. In summary, chronic intrathecal GM1 in doses up to 10 mg/d had no definable neuropathologic consequences.

Animals↗

PubMed2003

Ventricular haemodynamics in Python molurus: separation of pulmonary and systemic pressures.

Vascular pressure separation by virtue of a two-chambered ventricle evolved independently in mammals and birds from a reptilian ancestor with a single ventricle, and allowed for high systemic perfusion pressure while protecting the lungs from oedema. Within non-crocodilian reptiles, ventricular pressure separation has only been observed in varanid lizards and has been regarded as a unique adaptation to an active predatory life style and high metabolic rate. The systemic and pulmonary sides of the ventricle in Python molurus are well separated by the muscular ridge, and a previous study using in situ perfusion of the heart revealed a remarkable flow separation and showed that the systemic side can sustain higher output pressures than the pulmonary side. Here we extend these observations by showing that systemic blood pressure P(sys) exceeded pulmonary pressure P(pul) almost seven times (75.7+/-4.2 versus 11.6+/-1.1 cm H(2)O). The large pressure difference between the systemic and pulmonary circulation persisted when P(sys) was altered by infusion of sodium nitroprusside or phenylephrine. Intraventricular pressures, measured in anaesthetised snakes, showed an overlap in the pressure profile between the pulmonary side of the ventricle (cavum pulmonale) and the pulmonary artery, while the higher pressure in the systemic side of the ventricle (cavum arteriosum) overlapped with the pressure in the right aortic arch. This verifies that the pressure differences originate within the ventricle, indicating that the large muscular ridge separates the ventricle during cardiac contraction.

Animals↗